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| 舒芬太尼调节CXCL12/CXCR4信号通路对脑胶质瘤细胞恶性生物学行为的影响 |
| Influence of sufentanil on malignant biological behavior of glioma cells by regulating CXCL12/CXCR4 signaling pathway |
| 投稿时间：2024-05-11 |
| DOI：10.3969/j.issn.1000-0399.2025.03.006 |
| 中文关键词: 舒芬太尼 趋化因子CXC配体12 CXC趋化因子受体4型 脑胶质瘤细胞 恶性生物学行为 |
| 英文关键词: Sufentanil Chemokine CXC ligand 12 CXC chemokine receptor 4 Glioma cells Malignant biological behavior |
| 基金项目:河北省2023年度医学科学研究课题计划(编号:20232197) |
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| 中文摘要: |
| 目的 分析舒芬太尼对脑胶质瘤细胞恶性生物学行为的影响,并探讨趋化因子CXC配体12（CXCL12）/CXC趋化因子受体4型（CXCR4）在其中发挥的作用。方法 培养人脑胶质瘤细胞U251,将对数生长期细胞分为对照组、1μmol/L舒芬太尼组（1μmol/L）、5μmol/L舒芬太尼组（5μmol/L）、10μmol/L舒芬太尼组（10μmol/L）、AMD3100组即CXCR4抑制剂组（10μmol/L）、10μmol/L舒芬太尼+CXCL12组（10μmol/L舒芬太尼+100 ng/mL CXCL12）,倒置显微镜下观察细胞形态,CCK-8法测定细胞增殖能力,流式细胞仪测定细胞凋亡能力,Transwell小室法测定细胞侵袭、迁移能力,Western blot法测定B细胞淋巴瘤基因2（Bcl-2）、G1/S-特异性周期蛋白-D1（CyclinD1）、基质金属蛋白酶-2（MMP-2）、MMP-9、CXCL12、CXCR4蛋白表达。建立裸鼠异种移植瘤模型,分为模型组和舒芬太尼组,测量并记录小鼠体质量、肿瘤体积、重量及心、肝、脾、肺、肾的重量;Western blot法测定肿瘤组织中CXCL12、CXCR4蛋白表达;免疫组化法检测肿瘤组织Ki67表达。结果 与对照组相比,舒芬太尼低、中、高剂量组和CXCR4抑制剂组细胞皱缩,数量减少,细胞OD450、侵袭细胞数、迁移细胞数、CyclinD1、Bcl-2、MMP-2、MMP-9、CXCL12、CXCR4蛋白表达降低（P<0.05）,细胞凋亡率升高（P<0.05）;与10μmol/L舒芬太尼组比较,10μmol/L舒芬太尼+CXCL12组细胞数量增多,细胞贴壁性变强,细胞OD450、侵袭细胞数、迁移细胞数、CyclinD1、Bcl-2、MMP-2、MMP-9、CXCL12、CXCR4蛋白表达升高（P<0.05）,细胞凋亡率降低（P<0.05）。与模型组比较,舒芬太尼组肿瘤体积和重量、Ki67阳性率及CXCL12、CXCR4蛋白表达降低（P<0.05）,但体质量及心、肝、肾、肺、脾相对重量差异无统计学意义（P>0.05）。结论 舒芬太尼可能通过抑制CXCL12/CXCR4轴来抑制U251细胞增殖、侵袭、迁移,并促进U251细胞凋亡,这为舒芬太尼在脑胶质瘤中的应用提供新的可能。 |
| 英文摘要: |
| Objective To analyze the influence of sufentanil on the malignant biological behavior of glioma cells,and to explore the role of chemokine CXC ligand 12（CXCL12）/CXC chemokine receptor 4（CXCR4） in it. Methods Human glioma cells U251 were cultured,and cells in logarithmic growth phase were separated into control group,low concentration sufentanil group（1 μmol/L）,medium concentration sufentanil group（5 μmol/L）,high concentration sufentanil group（10 μmol/L）,AMD3100 group（10 μmol/L）,and high concentration sufentanil+CXCL12 group（10 μmol/L sufentanil+100 ng/mL CXCL12）.Cell morphology was observed under an inverted microscope.Cell proliferation ability was assessed by CCK-8 assay.Cell apoptosis was evaluated using flow cytometry.The ability of cell invasion and migration was measured by Transwell chamber method.The protein expression of cells G1/S-specific cyclin-D1（CyclinD1）,B-cell lymphoma gene 2（Bcl-2）,matrix metalloproteinase 2（MMP-2）,and matrix metalloproteinase 9（MMP-9）,CXCL12,and CXCR4 were determined by Western blot.Xenograft tumor models of nude mice were established and divided into the model group and sufentanil group.Weight,tumor volume and weight of heart,liver,spleen,lung and kidney of mice were measured and recorded.The expression of CXCL12 and CXCR4 in tumor tissues was determined by Western blot.The expression of Ki67 in tumor tissues was detected by immunohistochemistry. Results Compared with the control group,the number of U251 cells in the sufentanil low,medium and high dose groups and the CXCR4 inhibitor group decreased,the cells shrank,the cell OD450,number of invasive cells,number of migrating cells,the protein expression of CyclinD1,Bcl-2,MMP-2,MMP-9,CXCL12,and CXCR4 decreased（P＜0.05）,and the apoptosis rate increased（P＜0.05）;compared with the high-concentration sufentanil group,the number of cells in the high-concentration sufentanil+CXCL12 group increased,the cell adhesion became stronger,the cell OD450,number of invasive cells,number of migrating cells,the protein expression of CyclinD1,Bcl-2,MMP-2,MMP-9,CXCL12,and CXCR4 increased（P＜0.05）,and the apoptosis rate decreased（P＜0.05）.Compared with model group,the tumor volume and weight,the positive rate of Ki67 and the expression of CXCL12 and CXCR4 protein were reduced in sufentanil group（P＜0.05）,but the relative weight of body weight,heart,liver,kidney,lung and spleen had no significant changes（P＞0.05）. Conclusion Sufentanil may inhibit the proliferation,invasion and migration of U251 cells,and promote the apoptosis of U251 cells by inhibiting the CXCL12/CXCR4 axis,which provides a new possibility for the application of sufentanil in glioma. |
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